United Therapeutics Corp (UTHR) 2012 Q4 法說會逐字稿

Good morning, my name is Sammy and I will be your conference operator today. At this time, I would like to welcome everyone to the United Therapeutics Corporation fourth quarter and annual 2012 financial results conference call. All lines have been placed on mute to prevent any background noise. After the speaker remarks there will be a question-and-answer session.

(Operator Instructions)

Remarks today concerning United Therapeutics will include forward-looking statements which represent United Therapeutics expectations or beliefs regarding future events based on the current assumptions. United Therapeutics cautions that such statements involve risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements. Consequently, all such forward-looking statements are qualified by the cautionary language and risk factors set forth in the United Therapeutics periodic and other reports filed with the SEC. There can be no assurance that the actual results, events, or developments referenced in such forward-looking statements will occur or be realized. United Therapeutics assumes no obligation to update these forward-looking statements to reflect actual results, changes in the assumptions, or changes in factors affecting such forward-looking statements. Thank you. Dr. Rothblatt, you may begin.

Thank you, operator. Good morning, everybody, on the conference call. I am joined this morning by John Ferrari, our Chief Financial Officer; Roger Jeffs, our President and Chief Operating Officer; and Andy Fisher, our Chief Strategy Officer and individual in charge of Legal and Investor Relations. I'd like to start by making a few introductory remarks and then welcome any questions that could be directed to Andy, Roger, John or myself.

The press release that we issued this morning certainly makes this about as joyful a quarterly and annual conference call as any CEO could ask for. We're reporting record revenues, record profits, record profits per share. So, across the board, it's just been a fantastic quarter and a fantastic year for United Therapeutics. Our excellent annual results reflect both our leadership in pulmonary hypertension medicines and our discipline in focusing company resources on transformative growth opportunities. One of the things which is especially noteworthy is that as of the end of 2012 our medicines are now being prescribed to more pulmonary hypertension patients in the United States than any other company's medicines. That's a high watermark that we've achieved after our several years of slugging it out against other companies which are much larger and better capitalized than we. I think the reason for this is completely due to the fact that physicians, over time, have found that the United Therapeutics medicines are the ones that they can rely on to provide superior results for their patients.

Let me briefly mention what those medicines are, briefly mention some of their key highlights, and then say a word or two about our pipeline. And then, move into question-and-answers. Remodulin is a medicine which continues to grow now even though we are actually in the 10th year after its approval. But, is in a way like a kind of a version of a human being that they keep growing until they get to the Tween period, and then they just really burst out into becoming a full potential young adult. And, that is what you see here with Remodulin. It is the medicine that physicians reach for when patients are struggling with managing their pulmonary hypertension due to the oral treatments not being able to halt the progression of the disease.

It's interesting, I was in conversations with the leading physician the other day and he said to me, Martine, I know that the name Remodulin has nothing to deal with the fact that it seems to remodel the patients vasculature, but that is what it seems to do. And, that was just that physician's point of view, but it has certainly allowed patients to live a much more vigorous lifestyle than would be the case if they were not on Remodulin. What does Remodulin have going forward? Well, it's really exciting because what we have right now is a point where Remodulin is on the cusp of being approved in China.

It's about a year or so from being approved in Japan. And, intravenous Remodulin, which is -- generally doubles the number of patients who take Remodulin above subcutaneous Remodulin has just been approved in Europe. And, now we're getting country by country the pricing approvals necessary for us to begin commercializing it. So, we definitely expect a nice surge in Remodulin revenues from both the international opportunities for Remodulin as well as a continued confidence in physicians that the earlier they give patients Remodulin the better chance there is of perhaps having some favorable remodeling of the pulmonary vasculature.

Now, let me move into TYVASO. TYVASO is really like a horse in the -- that you see at the races who is right behind the lead horse, right behind the lead horse, pulls nose to nose and then pulls ahead. And, it's been exciting for us here at United Therapeutics to watch TYVASO gallup closer and closer to Remodulin. Right now TYVASO is literally nipping at Remodulin's heels. And, it doesn't really take a great expert at mathematical drawing of lines of growth to see that we are somewhere between 12 and 24 months for TYVASO to, in all likelihood, surpass Remodulin revenues and become the number one revenue generator here at United Therapeutics. Now, that is real exciting for us because one of our mantras that we have here in the company, and is driven by our desire to always make life better for the patients, is to make the older therapies seem to be relatively barbaric compared to the newer therapies. And, to always try to go for the next, next. What is the next, next?

The therapies that would work in the last decade, we're not a company that rests on those laurels. We're one that constantly pushes the ball forward. So, with TYVASO you can offer a patient who would otherwise be on a catheter 24 hours a day, and it's a hell of a lot better than being in a bed and these patients are able to do things from skiing and snow boarding, one patient ran for mayor, you name it. But, if you say to them what would you rather do, be on a catheter 24 hours a day or take four, two-minute inhalation sessions a day, everybody would choose the latter. And, it has taken a number of years for physicians to gain comfort with TYVASO having that kind of a potency because they have looked at Remodulin as the gold standard for so long, has been very cautious about taking a patient who might otherwise be prescribed Remodulin and instead prescribing them something which is such a different therapy like TYVASO.

It's a conservative field in pulmonary hypertension, and as 2010, 2011, 2012 rolled forward, we have now reached a point that there is a critical mass of physicians that will reach first for TYVASO whereas they would have previously perhaps reached first for Remodulin. And, that's especially true with regard to patients earlier and earlier in the disease process, the early New York Heart Association class III patients, even some of the late New York Heart Association class II patients. Physicians are gaining comfort with the fact that when you combine a PD-5 inhibitor and an ETRA with inhaled TYVASO, you are going to get a superior result. So, we are just really excited at this galloping of revenues on TYVASO and the trend lines which lead to it becoming our number one revenue producer within the next 12 or 24 months or so.

And now, let me speak about Adcirca. Adcirca is really something. It's a drug that was launched into competition against Pfizer. And, Pfizer had a very aggressive detailing force on the world's best-selling drug, Viagra, which was rebranded as REVATIO for pulmonary hypertension. Despite that effort, we are, of course, a small biotech company and nowhere near the resources of Pfizer, yet our great partners Lilly had faith and confidence in us and gave us all manner of scientific and clinical trial support. And, as a result of that, we have the data that has been able to demonstrate to physicians that they are better off putting their patients on Adcirca than REVATIO.

That data starts with the fact that Adcirca needs to be dosed just one time a day compared to REVATIO, or it's generic -- in it's generic form Sildenafil, having to be dosed three times a day. But, when you're dealing with a life-threatening illness with patients having just a few years of life, and this is not a place to pinch pennies and hoping that the patient will remember their middle of the day and the end of the day dose, because if they don't there would be serious consequences for the patient's health. So, given the relative affordability of Adcirca in the first place, it's not surprising to me that -- just to share with you some data I got from Dr. Jeffs in January, we crested 12,000 prescriptions written for Adcirca in January which is the highest ever. And, many people believe there is something like 25,000 patients with pulmonary hypertension. That means almost 50% of all patients are prescribed Adcirca alone, not to mention our other drugs. And, I really am very, very pleased that our sales and marketing teams see this not as a resting point but as a launching pad. And, indeed, our goal is to continue to bring the benefits of Adcirca to the physicians until we can get 15,000 and even 20,000 prescriptions for Adcirca in the coming years.

I promised to say a couple words about our pipeline. Let me just highlight two programs in particular. Though, I'll touch actually on the three because I didn't really complete the story on Remodulin as the third. Remodulin has, in addition to its international sales potential, it has a new sales potential that's about to pop out through the miracle of some technology called implantable pump technology. This technology has miniaturized the type of outside the body pumps that our patients wear until they are so small, and so -- and made of such materials that are so biocompatible with the cardiovascular spaces of the human, that they can be implanted inside the body in an outpatient, minimally invasive procedure. Implanted inside the abdomen, I'm sorry, and continue to gradually seep, s-e-e-p, seep Remodulin out of a tiny specialized catheter built into the device 24 hours a day, 365 days a year.

So, we expect to fully enroll -- we have already fully enrolled our implantable pump program with Medtronic and we expect to report the results of that out in August of this year. And, by the way, a little sign of how well that study is going, the original target date to report the results was October, then it was September, and then it was August. I have never experienced something like this in my years as a drug developer, a program that was ahead of schedule, and a clinical trial that was finishing sooner. And, the reason for this is that the duration of the incredible pump program is based on accumulation of a certain number of years of patient years of safety. And, there have been so few dropouts from the implantable pump program. They had predicted that there would be a certain number of dropouts, so it was results in October.

But, there have been so few that we are now scheduled to accrete -- accumulate all the safety data we need by August. Just absolutely remarkable. And, I have heard the stories from the patients and certainly not a surprise to me why they would -- nobody would want to drop out. It's a life giver-backer to the patients. The patient's say our life has been given back to us. We have no pump outside our body, no catheter. This implantable thing, I visit the doctor once every one to two months depending on the patient. They fill it up, and I'm good to go. It's really remarkable.

So, that's in our pipeline but that should be popping into commercialization in late 2014 early 2015 time frame. The other two things I really wanted to mention is oral Treprostinil which we continue to be very, very excited about. We've got a gangbuster clinical trial going on right now. Be enrolling over 850 patients, all of the major pulmonary hypertension centers in the world are participating in this study.

We believe it's going to result with a statistically significant outcome showing a delayed clinical worsening when oral Treprostinil is dosed in combination with other drugs which will certainly validate the blockbuster potential for that drug. In the meantime, even as a mono therapy, we have our filing before the FDA, accepted resubmission, as many of you have seen in the previous press release, and that's pending FDA review right now. Of course, those of you who have been UT watchers, or I may say unitherians for a few years, you know we have a policy of not commenting on matters that are under FDA review. We certainly are going to extend that policy to cover oral Treprostinil at this time.

The second big exciting thing in our pipeline is the transcontra proximal program. This program we announced several months back. We've had some fantastic progress on the chemistry manufacturing controls side of that project. That project will allow us to ultimately take the magic of Remodulin and reduce it, when combined with a couple of additional molecules, to a once daily, 10-second injection, subcutaneous, no site pain, and get the benefit of a zero order release like Treprostinil over a 24-hour period. This is a therapy which is so transformational, it's exactly what I mean in the press release when I talk about transformational opportunities, that it actually harkens to the day when all pulmonary hypertension patients will be able to avail themselves not only of Treprostinil, which is great, but a zero order release delivery of Treprostinil. Meaning like a level dosage of it in their bloodstream 24 hours a day, which is the best of the best.

So, with those introductory remarks, let me now open up the phone lines to any questions to Dr. Jeffs, John Ferrari, or Andy Fisher. Operator?

Thank you.

(Operator Instructions)

Mark Schoenebaum, ISI Group

Hey, Martine.

Could you just maybe explain to us why you made a decision to refile the Oral Treprostinil NDA, if that's possible to comment on that?

Sure, definitely. That's -- that, to me, is a favorite topic.

I think, really, that to not refile it would be the absolute worst decision I might have ever made as CEO of the Company. We're talking, Mark, about a molecule that has been a lifesaver for thousands of patients. It's the key pharmaceutical ingredient in Remodulin. It's the API in Tyvaso. In all of its clinical trials it resulted in P values which were either statistically significant, in the case of the Freedom-M trial, or very close to statistical significance in the case of the Freedom C1 and C2 trials.

And, as I know you know very well, Mark, statistical significance 0.05 is not some magic marker in the sense that a drug definitely positively works if it is less than 0.05, and definitely possibly does not work if it's above 0.05. It's instead a regulatory line in the sand, and can be somewhat of a shaded line in the sand depending on compelling factors to take into account, especially for patient welfare. So, the P values for the C1 and C2 studies were so close to statistical significance nobody doubted that the drug works. Nobody thinks that the drug is a placebo. And, in fact, when you begin to look at subsets of the patients, have a dramatic benefit for many of the patients.

With regard to the Freedom-M data, Oral Treprostinil had a better demonstration of efficacy with high statistical significance than Remodulin or Tyvaso did. Again, just what I'm talking about here, it's six-minute walk outcomes, which were greater for Oral Treprostinil than for Tyvaso or Remodulin. As you see from our financial results today, Mark, Remodulin is far and away the first choice of physicians for prostacyclin therapy delivered parentially. Tyvaso is far and away the choice of physicians for prostacyclin therapy delivered via inhalation.

Both of them continue to be prescribed by physicians to ever greater numbers of patients. So, of course, we are going to refile Oral Treprostinil. And, of course, we're going to be relentless in getting this drug approved because sooner or later it will get approved and it will be a great blessing to the patients who have it.

And what is your level of confidence that will be approved? And then I'll drop off.

I think that I personally am a believer in the right things and the right outcomes resulting, so long as one doesn't quit and give up first. So my personal belief is, as long as we persistently do everything which is right and necessary, Oral Treprostinil definitely will get approved. And I know it sounds silly to say quitters never win and winners never quit, but we are winners here and we are not going to quit on Oral Treprostinil.

Thank you.

Michael Yee, RBC Capital Markets.

Good morning. This is John on behalf of Michael Yee.

Understanding the need to keep comments in general, can you describe to us the contingencies for outcomes with patent infringement case with Sandoz? And with the court case beginning, could you just clarify for us when the Markman summary judgments could come? Is it before year end? Thank you.

Sure, thank you for the question from RBC Capital. I am going to bounce that question over to our patent guru, Andy Fisher.

Thanks Martine. And, thanks for the question, John.

Just to review a little bit, we filed a lawsuit against Sandoz about a year ago after receiving a Paragraph IV notification related to their ANDA filing. That case is currently underway and proceeding pursuant to a scheduling order entered by the court early last summer. The scheduling order is available through the court docket system if anyone cares to review it. It sets a pretty specific calendar with specific time frames for different activities to occur. Right now, we are in the pre-Markman briefing phase. And the court, I believe, will hold a scheduling conference in the spring to set the format and timing of the actual Markman hearing, which should take place, I think, sometime in Q2. Following that, the calendar specifies things such as briefing on summary judgment motions, and for those to conclude sometime in early 2014. And then we'll set a trial date sometime later in -- probably the mid-2014 timeframe. So, that's the general calendar. And, like I said, everything so far has proceeded pursuant to the calendar set by the court.

As far as speculating on different outcomes, that's something we're really not going to comment on. I think all of you who are experienced pharma and biotech investors know what the potential outcomes of cases like these are. And same rules apply to pretty much every case. We have said from the outset that we are very confident in the intellectual property we have protecting this product, and intend to enforce that IP vigorously as we proceed through the case.

Thanks, Andy, great answer. Next question?

Liana Moussatos, Wedbush Securities.

Thank you.

When you received the complete response letter for Oral Treprostinil, it sounded like the expectation was having to redo another trial before resubmitting. When you went back and looked at the data, did you see something new that you had not seen before that caused you to resubmit so soon, or recently?

Liana, thanks for your question, and thanks for your excellent analyst coverage of our company as well over so many years past. As noted, we really don't want to get into discussing internal discussions with the FDA out of respect for the regulatory process and the PH community in general. But, as Roger is in charge of this entire effort -- Roger would you like to provide any overall color that could be responsive to Liana?

Sure, Martine, thanks for the question, Liana, and good morning.

Maybe I will just start with a topical response in that, in science there are no absolutes, and different people can address the same scientific data set and reach different conclusions. And certainly that came into play here -- that when we got the complete response letter that was our first view of some of their science at the Cardio-Renal division -- scientific conclusions on our NDA submissions.

Subsequent to that, we had a face-to-face and a review meeting in December, where we were able to respond to the questions and inform them about the rationality of our responses and why the data set made sense, particularly as an alternative dosage form. I think based on that favorable meeting, which we think was informative and even didactic at certain periods of time, a resubmission was felt to be warranted both by us and the division. And, therefore, we did do the resubmission, which was viewed as a complete response to all of the issues that were [gaiting] in the complete response letter.

And, as Martine has said, we won't comment on further discussions to that point, but I think you are correct that most of what we have shown them is perhaps re-analysis, or re-emphasis, on analyses that we did previously and not new data. So the resubmission was accepted without the need for new data.

I think that's all I'll comment; otherwise I'll start getting into details.

Thank you very much.

Thanks Liana. Thanks, Roger. Operator, next question

Eun Yang, Jefferies.

Thank you.

Question on Remodulin. Since the Tyvaso launch, Remodulin annual growth has been mid to high single digits versus in 20%s previously. Can you tease out how much impact is due to -- the decline in annual growth, is it due to Tyvaso versus Remodulin being a mature product?

It's an interesting question and thanks for asking it.

I think a certain part of the -- it's like what Roger said previously; there is many different ways to view those numbers. And so I'm going to give you a 360-degree answer, if you'd like, taking a look at the same numbers from different perspectives.

First of all, there is a factor of just the law of large numbers at play here. And as the base gets larger and larger incremental revenues are going to represent a smaller percentage of growth period to period. So there's a certain factor of law of large numbers at work here.

That factor is not so important when one has a very wide, essentially unlimited or barely tapped, addressable and capturable market. But, with the case of subcutaneous and intravenous Remodulin, we may be coming very close to the size of the addressable market. Physicians report a certain amount of resistance on the part of patients to putting up with the rigmarole associated with having a catheter, either sewn or often painfully inserted into their body, hooked up to a pump that they have to carry around, sleep with, live with 24 hours a day. And, in the case of the intravenous Remodulin, comply with extremely stringent infection control and sterility procedures.

It's a big burden. And, there's no doubt about it, we're dealing with an orphan disease population in the first place -- probably just about 25,000 diagnosed and treated patients in the US. And of those, the patients who would be willing to put up with this kind of a rigmarole, are going to be the most sick of the patients, given that there are other therapies available that can be taken orally. Generally speaking, the most quoted statistic that you will see is that something like 10% to 15% of the patients are what are called New York Heart Association Class IV. So, that would be, maybe let's say, 3,000 patients upwards of that.

And UT Remodulin sales, probably from a dollar standpoint, we probably account for about 75% of the dollars spent on parental prostacyclins already. So that's another factor in terms of the growth rate. When you're getting very close to the ceiling of where you can grow, there's not that much -- if you keep going at double-digit rates you're just going to crash into the ceiling. So, it's natural process that growth rate slow down once the room for growth becomes diminished.

With regard to the transition between Flolan and Remodulin, there is a certain amount of that at play, but there is also a certain amount in the other direction. So, I'm not sure if it's really a factor because it may just be a wash. There are a certain number of patients that transition from subQ or IV Remodulin onto Tyvaso. And, I think that was behind your question, if that was a result of some of the diminishment in the growth rate of Remodulin. But, there are also a certain number of patients that transition from Tyvaso to subQ or IV Remodulin. And, I think it's probably a wash there, and that, that factor does not really account for the single-digit growth rate on Remodulin. I think it's more of a law of large numbers and the fact that we're maxing out on the addressable demand for subQ and IV therapies.

With regard to Tyvaso, you see that therapy galloping forward. It's not at the expense of Remodulin; it's because that therapy, as I mentioned in my introductory remarks, has -- it's taken two or three years, quite naturally, for it to gain confidence among physicians as a therapy that has wide applicability throughout the New York Heart Association Class II and New York Heart Association Class III ranges of patients.

Now, it's generally thought that the Class II and the Class III patients combined represent probably 75% of the marketplace. So, let's say conservatively, 15,000 out of those 25,000 diagnosed patients are Class II and Class III patients. As of right now we have something like 3,000 patients on Tyvaso. So there is a lot of headroom -- just the opposite situation with Remodulin -- there's a lot of headroom for Tyvaso to grow. And, the space for Tyvaso to grow is not limited in the same way it is as Remodulin. And hence it's entirely foreseeable that Remodulin's revenues will continue to grow at a single-digit rate, but that will not stop Tyvaso's revenues from growing at a much faster rate. And hence it's predictable that Tyvaso will, in the near-term, become the largest source of revenues for United Therapeutics compared to Remodulin.

I hope that was responsive to your question.

Yes, thanks, very much. That's very helpful.

Quickly, on Tyvaso, can you --.

Unfortunately, it's a long queue, so we have to have it one question per questioner policy. Operator, next question.

Sure.

Phil Nadeau, Cowen and Company.

Good morning, thanks for taking my question.

Martine, in your pipeline update you didn't mention your neuroblastoma antibody. Could you give us an update on the status of the antibody and how big of a market opportunity you think it could address? Thanks.

Okay, great.

Well, thanks a lot for the question from Cowen, and we certainly look forward to presenting at your company's event next week. And, I'd like to ask Roger, who is managing the neuroblastoma program, to kindly respond to your question.

Yes thanks for the question Phil. Happy to answer it.

Again, for some background, our antibody C14.18 is a monoclonal antibody that binds to a lipid called GD2 on the surface of the neuroblastoma cells. An, for those who may know, neuroblastoma is a cancer of the peripheral nervous system and responsible for about 12% of all deaths due to cancer in children under 15, with about 50% of the patients with neuroblastoma having what's called a high risk form of the disease, with very poor long-term prognosis and survival rate.

There was a trial by NCI that showed improved survival. Subsequent to that trial, NCI has also recently completed a 105-patient safety and toxicity study with the antibody. And what we have done is acquired the rights to manufacture and commercialize C14.18 for the market. We are in late stage process validation work; so we have done, I would say, 95% of the work that we need to do. There is certainly more work to do. But we are in the submission build phase now, both for the US and Europe.

And it is our intention to file, based on discussions with both the US and EU regulatory authorities later this year. So that would suggest that this therapy would be approved sometime in 2014. So we're very pleased with the capability that our manufacturing team in Silver Spring and their ability to progress the process and the scale-up of the antibody production. And we look forward to supporting this new market.

Great. And, do you owe NCI a royalty?

I'm sorry, Phil?

Do you owe NCI a royalty on sales?

No, it was a license fee. Straight out, basically.

Okay, great. Thanks for taking my question.

Next question, Operator.

Terence Flynn, Goldman Sachs.

Thank you, this is Alicia [Longbacher] in for Terence Flynn. And, thank you for taking our question.

Just a question on the ongoing Freedom-EV trial. Have you made any changes to the protocol?

Roger, would you like to answer that question?

Sure. Again, for background, as Martine alluded to earlier, Freedom-EV is our long-term time to clinical worsening study of Oral Treprostinil added to background therapy; just single background therapy. In patients with pulmonary hypertension they must be newly diagnosed with a duration of background therapy of no shorter than 30 days and no longer than one year. So we're going to follow those patients for several years and observe the time to clinical worsening and see the impact of Oral Treprostinil on top of a single background therapy.

That study is enrolling. We plan to complete the study enrollment in 2014. And that would suggest a completion and un-blinding of that study in the first half of 2016. It's a global study. We have over 125 sites that we are initiating. And we're very pleased with the progress that we are making in that front.

We have made -- and with all protocols over their lifetime, there are amendments that go on. In fact, I think when we look back to our original Freedom-M and Freedom-C and C2 studies, we had over five amendments.

So, similarly here we have an amendment to the protocol that has tweaking different aspects of the protocol, including some endpoint definitions, as well as introducing a different dosing strategy. Again that's normal throughout the course of development and there will be further amendments I will predict now, or actually guarantee, over the next three to four years as we complete this protocol.

Thanks, Roger. Operator, I think we have time for one more question.

Geoff Meacham, JPMorgan.

Another good quarter, Martine; thanks for taking my question.

Our pleasure, Geoff. Good to hear your voice this morning.

So, I guess a follow-up on Freedom-EV. Is there a plan to design a formal interim analysis on this study? Do you feel like this could help to the ongoing FDA review of oral?

And then, just a real quick one on Tyvaso. Could you talk about the new TD-100 device -- how you think it's different relative to the current one? Thanks.

Okay, Geoff. Well, let me ask Roger -- if you don't mind, Roger, to answer both of those questions, and then I'll wrap up.

Yes, on the TD-100 -- that's the device that has improvements that were somewhat FDA-mandated at the time of approval. So we had a post-marketing commitment to do certain things, like put an alignment key on the dome and the base, and other aspects. So we've completed that. So those improvements were done, approved in late 2012. And we're launching that into the market, basically the next quarter. So we will be transitioning our patients to this newer device.

I would also say that we're in development of a third-generation device, which we're actually calling the Gen-3 device, which is a further improvement in same mechanical aspects so it won't require any new studies. But it's a miniaturization of the device, an improvement of the device; and an improvement in particular in its intelligence, if you will, so that we can look at patient compliance and adherence.

The question on Freedom-EV -- if you could remind me what that was again?

Yes, is there a plan -- I know one of your competitors has an interim analysis on their study. I'm wondering if it's possible with the current powering assumptions to design that into Freedom-EV? And do you think that could help out the ongoing FDA review if there is a more nearer-term data disclosure?

Yes. In terms of an interim, we don't plan to do a study -- interim analysis. We are enrolling over 850 patients to accrue approximately 400 events. The difficulty with an interim -- by the time that you collect the data to do the interim analysis, you've almost enrolled the complete study population. So, it becomes a bit of a statistical waste of power. So it's not something we are keen to do. But, I appreciate that other people are doing it, because I think they vaulted their sample size further. So they must be worried about event rate.

But we will evolve that thinking as we go; but currently there is no plan to do that. As it relates to the current application -- as we said, we resubmitted the NDA based on the merits of the original filing. And we continue to believe that the merits of that original filing warrant approval. And we'll know likely within about five weeks time what the outcome of that discussion is. And then we can, based on the outcome, we can then figure out how to move forward with Freedom-EV either as part of the solution or as part of the market expansion.

Okay, thanks.

Thanks, Roger. Thank you, everybody, for your questions this morning.

We're moving around to the halfway mark after the start of the question period. So, let me wrap up that we appreciate the opportunity to share our annual and quarterly results with you. Very pleased to be able to share such great results with you. All three of our products continue to do very well as we round 2012 and start off in 2013.

Remodulin -- we expect continued growth from Remodulin in the very near term from international opportunities -- Japan, China, and Europe. And, in the medium term from the new implantable pump once that receives label expansion from the FDA. That, we think, has the prospects to as much as double the size of the Remodulin market.

We expect continued growth in Tyvaso, in part because we are seeing the signs of greater than ever confidence and interest in physicians. And we are expecting an inflection point with a faster uptake in growth starting this year. And also because of the factors that Roger just walk us through in terms of the second-generation and even third-generation inhalation devices making that therapy easier and easier to use.

And then finally, with regard to Adcirca, we have surpassed all competitive therapies in terms of that being the most-prescribed drug for pulmonary hypertension. And instead of this being any kind of a plateau, we actually just see it as a launching pad for yet greater growth, and the high likelihood that Adcirca will be continue to be the foundational therapy for pulmonary hypertension.

We have a really exciting pipeline. Roger talked about the Freedom-EV study and I touched on the TransCon Treprostinil. There other exciting things in our pipeline. We talked about the 14.18; got some exciting antiviral opportunities in our pipeline. And another entire prostacyclin platform based on the [bare] prosta molecule, both in its sustained-release and also in its TransCon formulation.

So -- great pipeline, great currently marketed products. We're really excited to be doing so much for the pulmonary hypertension patients in the community. And, thank all of you for your support and interest in United Therapeutics. Have a great day.

Thank you for participating in today's United Therapeutics Corporation fourth quarter and annual 2012 financial results earnings conference call. This call will be available for replay beginning at 11.30 AM Eastern Standard Time through 11.59 PM Eastern Standard Time through March 5. The conference ID number for the replay is 89593584. The number to dial in for the replay is 855-859-2056 or 404-537-3406. Everyone, have a great day.